Active-site-directed reagents will be synthesized satisfying the specificity of trypsin. These will be evaluated as inactivators of the trypsin-like enzymes, thrombin, plasmin, and kallikrein. An attempt will be made to devise selective inhibitors capable of inactivating each of these enzymes without acting on the other two. The reagents will be of two types: chloromethyl ketones derived from lysine or esters which, acting as poor substrates, arrest catalytic action at an acyl-enzyme stage. The proteolytic cleavages involved in the growth of mouse EMC virus will be studied in ascites cells in the hope of characterizing the responsible enzymes and devising inhibitors for them.